title: The effects of L-deprenyl treatment, alone and combined with GM1 ganglioside, on striatal dopamine content and substantia nigra pars compacta neurons.
abstract: The present study examined the effects of GM1 ganglioside and the monoamine oxidase B (MAO-B) inhibitor L-deprenyl, alone and in combination, on striatal dopamine (DA) and DOPAC levels, and the density of tyrosine hydroxylase (TH) positive neurons in the substantia nigra pars compacta (SNc) of C57bl/6J mice following MPTP administration (20 mg/kg, s.c., twice daily for 5 days). GM1 treatment (30 mg/kg, i.p., daily for 3 weeks, beginning 24 h after the last MPTP injection) partially restored striatal DA levels and rescued SNc neurons. A high dose of L-deprenyl, inhibiting MAO-B activity, (10 mg/kg, i.p. every other day for 3 weeks beginning 3 days after the last MPTP injection) increased striatal DA content, but did not rescue TH-positive SNc neurons. A low dose of L-deprenyl (0.01 mg/kg, i.p. every other day for 3 weeks beginning 3 days after the last MPTP injection) had no effect on either striatal neurochemistry or the rescue of SNc TH-positive neurons. Co-administration of GM1 and high dose L-deprenyl caused a synergistic increase in striatal DA levels, above that obtained with either GM1 or high dose L-deprenyl alone. Co-administration of GM1 and low dose L-deprenyl was not only not synergistic, but caused GM1s effects to be antagonized. The results do not confirm previous findings that low dose L-deprenyl administration in vivo after MPTP can rescue SNc neurons. Given GM1's potential as an adjunct to present anti-parkinsonian medications which include L-deprenyl, it will be important to further investigate the interactions between these two potential therapies.
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Rothblat
authors.forename: J S
authors.initials: JS
authors.lastname: Schneider
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D005677:G(M1) Ganglioside; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine